John Danesh
University of Cambridge
Publications 368
#1P. Akbari (BHF: British Heart Foundation)
Last.Michel Georges (University of Liège)H-Index: 66
view all 33 authors...
Thousands of genetic associations with phenotypes of blood cells are known, but few are with phenotypes relevant to cell function. We performed GWAS of 63 flow-cytometry phenotypes, including measures of cell granularity, nucleic acid content, and reactivity, in 39,656 participants in the INTERVAL study, identifying 2,172 variant-trait associations. These include associations mediated by functional cellular structures such as secretory granules, implicated in vascular, thrombotic, inflammatory a...
#1Johannes KettunenH-Index: 45
#2Michael V. HolmesH-Index: 32
Last.Mika KähönenH-Index: 80
view all 22 authors...
1 Citations
#1Johannes Kettunen (National Institute for Health and Welfare)H-Index: 45
#2Michael V. HolmesH-Index: 32
Last.Mika Ala-KorpelaH-Index: 47
view all 22 authors...
Cholesteryl ester transfer protein (CETP) inhibition reduces vascular event risk, but confusion surrounds its effects on low-density lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic inhibition of CETP on detailed lipoprotein measures and compare those to genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We used an allele associated with lower CETP expression (rs247617) to mimic CETP inhibition and an allele associated with lower HMGCR expressio...
#1Scott C. RitchieH-Index: 5
#2Yingying LiuH-Index: 3
Last.Michael InouyeH-Index: 43
view all 18 authors...
Polygenic risk scores (PRSs) capture the polygenic architecture of common diseases by aggregating genome-wide genetic variation into a single score that reflects individual9s disease risk, affording a new opportunity to identify downstream molecular pathways involved in disease pathogenesis. We performed an integrative analysis to characterise associations of PRSs of five cardiometabolic diseases with 3,442 plasma proteins in 3,175 healthy individuals. Through polygenic association scans we iden...
#1Alexander TeumerH-Index: 70
#2Yong Li (University of Freiburg)H-Index: 26
Last.Anna Köttgen (Johns Hopkins University)H-Index: 52
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Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an ind...
#1Gad Abraham (University of Cambridge)H-Index: 14
#2Rainer Malik (LMU: Ludwig Maximilian University of Munich)H-Index: 36
Last.Martin Dichgans (LMU: Ludwig Maximilian University of Munich)H-Index: 5
view all 10 authors...
Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22–1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset...
3 CitationsSource
#1Laura B. L. Wittemans (University of Cambridge)H-Index: 3
#2Luca A. Lotta (University of Cambridge)H-Index: 14
Last.Claudia Langenberg (University of Cambridge)H-Index: 88
view all 23 authors...
Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not pr...
4 CitationsSource
#1Marijana Vujkovic (UPenn: University of Pennsylvania)H-Index: 13
#2Jacob M. Keaton (Vandy: Vanderbilt University)H-Index: 6
Last.Danish Saleheen (Columbia University)
view all 46 authors...
We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations...
#1Dirk S. PaulH-Index: 21
#2David StaceyH-Index: 4
Last.John DaneshH-Index: 106
view all 7 authors...
Population-scale genomic analyses have transformed our understanding of the contribution of genetic variation to the risk of cardiovascular disease. However, a major challenge in unlocking the pote...
#1Brian A. Ference (University of Cambridge)H-Index: 19
#2Deepak L. Bhatt (Brigham and Women's Hospital)H-Index: 122
Last.Marc S. Sabatine (Brigham and Women's Hospital)H-Index: 90
view all 18 authors...
Importance The relationship between exposure to lower low-density lipoprotein cholesterol (LDL-C) and lower systolic blood pressure (SBP) with the risk of cardiovascular disease has not been reliably quantified. Objective To assess the association of lifetime exposure to the combination of both lower LDL-C and lower SBP with the lifetime risk of cardiovascular disease. Design, Setting, and Participants Among 438 952 participants enrolled in the UK Biobank between 2006 and 2010 and followed up th...
12 CitationsSource